tbuckley/cabot-search huggingface dataset:
Efficacy and safety of nab-paclitaxel+cisplatin/nedaplatin + S-1 as an induction chemotherapy regimen for locally advanced hypopharyngeal cancer.
Authors: Cailing Jiang, Xiaosong He, Lieyin Xu, Shengyuan Xu, Yunyan Mo, Mafei Kang, Lin Zhu, Feng Xue
Journal: Journal of Clinical Oncology (2023)

e18050 Background: Targeted therapy and immunotherapy are efficacious treatment options for advanced head and neck cancer. However, the treatment of locally advanced hypopharyngeal carcinoma still consists of surgery, radiotherapy, and chemotherapy. Combining docetaxel, cisplatin (DDP), and 5-fluorouracil as standard induction chemotherapy provided opportunities for further surgical larynx preservation in some patients. This study retrospectively analyzed the short-term efficacy and adverse events of nab-paclitaxel + DDP/nedaplatin (NDP) + S-1 as an induction chemotherapy regimen for locally advanced hypopharyngeal cancer. Methods: The study included 22 patients with locally advanced hypopharyngeal cancer treated via induction chemotherapy at the Affiliated Hospital of Guilin Medical University from December 2020 to July 2022. Among these patients, 11 received nab-paclitaxel (125mg/m 2 , days 1 and 8) + DDP (35- 40mg/m 2 , days 1-2) or NDP (65-75mg/m 2 , day 1) + S-1 (30-40 mg/m 2 bid, days 1-14) every 21 days for a total of three cycles. A baseline enhanced magnetic resonance imaging (MRI) of the head and neck was performed for all patients to confirm the presence of suspicious lesions. Another MRI was performed before the third cycle of induction chemotherapy to confirm the efficacy of the treatment regimen. Patients, who were responsive to the induction therapy, were allowed to choose their respective sequential therapy regimen. The response was assessed using RECIST v1.1. Adverse reactions were evaluated according to CTCAE5.0. Results: The response to treatment of the 11 patients was assessed by the investigators. There was one patient with a complete response (9.1%), eight patients with a partial response (72.7%), and two patients with stable disease (18.2%). The objective response rate was 81.8% (9/11), and the disease control rate was 100%. Five of the nine patients with a partial or complete response opted for surgery after three cycles of induction chemotherapy. The pathological complete response rate was 100% (5/5). The most common grade 3 treatment-emergent adverse events (TEAE) were leukopenia (45.5%), neurotoxicity (36.3%), and anemia (18.2%). Grade 4/5 TEAEs were not observed. Conclusions: Based on the results of this retrospective study, the nab-paclitaxel + DDP/ NDP + S-1 was a safe and viable induction chemotherapy regimen for locally advanced hypopharyngeal cancer. It allowed more options for subsequent treatment. Further research is warranted to validate the findings of this study. [Table: see text]
Receipt of financial drug assistance for oral targeted therapy among older adults with advanced non-small cell lung cancer (NSCLC).
Authors: Anika Kumar, Meera Vimala Ragavan, Sandra Zeng, Melisa L. Wong
Journal: Journal of Clinical Oncology (2023)

e18916 Background: Financial drug assistance programs are a critical resource to mitigate financial toxicity for oral targeted therapy but can be challenging to access and navigate. Older adults with cancer frequently face high copayments for oral targeted therapy, yet they may be less able to navigate assistance programs due to functional and cognitive impairments. To identify potential barriers to receipt of assistance among older adults with advanced NSCLC, we evaluated associations between demographic, clinical, and geriatric assessment characteristics and receipt of financial drug assistance. Methods: We conducted a prospective cohort study at a Comprehensive Cancer Center where thoracic oncology nurses and pharmacists are available to help patients navigate financial drug assistance applications. We enrolled adults age &gt; 65 with advanced NSCLC starting a new chemotherapy, immunotherapy, and/or oral targeted therapy regimen with non-curative intent. For this analysis, we included only older adults who received oral targeted therapy. Patients completed a pretreatment geriatric assessment to evaluate function, cognition, social support, comorbidities, mood, and nutrition. Receipt of financial drug assistance was abstracted from the medical record. We used Fisher’s exact tests to evaluate for differences in demographic, clinical, and geriatric assessment characteristics between those who did and did not receive financial drug assistance. Results: Of the 168 older adults with advanced NSCLC in the parent cohort study, 45 received oral targeted therapy and were included in this analysis. Median age was 74 (range 65-94); 56% were White, 40% Asian, 2% Black, and 2% Hispanic. The majority had Medicare (76%) followed by private insurance (18%), Medicare and Medicaid (4%), and Medicaid alone (2%). On the geriatric assessment, 60% were dependent in instrumental activities of daily living, 20% were dependent in basic activities of daily living, 51% had an abnormal Montreal Cognitive Assessment, and 42% had poor tangible social support. Overall, 9 older adults (20%) received financial drug assistance for their oral targeted therapy. Older adults with a lower household income were more likely to receive financial drug assistance (p = 0.007). There were no statistically significant differences in receipt of financial drug assistance according to other demographic, clinical, or geriatric assessment characteristics including function, cognition, and social support. Conclusions: Older adults with advanced NSCLC on oral targeted therapy with lower household incomes were appropriately more likely to receive financial drug assistance. The lack of associations between receipt of financial drug assistance and function, cognition, and social support suggests that thoracic oncology staff are successfully helping older adults navigate financial drug assistance programs.
Effect of COVID-19 on mortality in patients admitted for DVT/PE with pre-existing cancer diagnosis at the beginning of the COVID-19 pandemic: A national inpatient sample study.
Authors: Andrew Campbell, Ziad Abuhelwa, Danae M. Hamouda
Journal: Journal of Clinical Oncology (2023)

e18903 Background: Coagulopathy and thrombosis are commonly associated with both cancer and Coronavirus Disease 2019 (COVID-19) infection. Thus, it is thought that cancer patients with COVID-19 carry an even higher risk for thrombosis than each disease individually. Cohort studies using the COVID-19 and Cancer Consortium (CCC19) registry data have identified risk factors for development of in-hospital VTE and PE in patients with cancer and COVID-19, however the risk of in-hospital mortality and length of stay in this population remains unknown. Using newly-available data from the National Inpatient Sample in 2020, we compared rates of in-hospital mortality and length of stay between patients with and without COVID-19 infection admitted for DVT and PE with known diagnosis of cancer. Methods: The National Inpatient Sample was analyzed to identify all adult admissions with primary diagnosis of DVT and PE and secondary diagnosis of solid tumor or hematologic malignancy from April to December 2020. These patients were then stratified based on secondary diagnoses of COVID-19 infection. Rates of inpatient mortality and hospital length of stay were compared to non-COVID patients. The cases for COVID-19 infection, thrombotic events, and cancer were selected based on ICD-10 (International Classification of Disease) codes. ICD-10 codes used for solid tumor malignancies included breast, lung, prostate, colon, pancreas, liver, and rectal cancer. ICD-10 codes for hematologic malignancy included leukemia, lymphoma, and multiple myeloma. Chi square tests were utilized to check the significance of association between mortality, LOS and COVID-19 infection in the population admitted for DVT and PE. Results: There were a total of 13,856 patients admitted for DVT/PE with secondary diagnosis of solid tumor or hematologic malignancy from April to December 2020. Among this population, 80 patients (mean age 61 years) also had a secondary diagnosis of COVID-19 infection. Overall in-hospital death rate for cancer patients with DVT/PE was 5.2% (n = 720). Less than 1% (n = 5) of those patients had a secondary diagnosis of COVID-19 infection (P = 0.8547). Mean LOS with COVID-19 diagnosis was 4 days (95% CI 2.7 - 5.3) and without COVID diagnosis was 4.75 days (95% CI 4.5 - 5, P = 0.4483), showing no statistically significant difference. Conclusions: There was no statistically significant difference of mortality or LOS between COVID-19 and non-COVID-19 infected patients admitted for DVT or PE with secondary diagnosis of malignancy.
Analysis of different color unmixing methods for cMET-PDL1-EGFR multiplex assay.
Authors: SATARUPA MUKHERJEE, Nahil Sobh, Jim Martin, Yao Nie, Erika Walker, Terry Landowski
Journal: Journal of Clinical Oncology (2023)

e21080 Background: Multiplex brightfield imaging offers the advantage of simultaneously analyzing multiple biomarkers on a single slide, as opposed to single biomarker labeling on multiple consecutive slides. To accurately analyze multiple biomarkers localized to the same cellular compartment, a set of common lung panel markers were selected as a model, cMET-PDL1-EGFR. One of the most crucial preliminary stages for analyzing this assay is identifying the unique chromogens on individual cells. This is a challenging problem due to the co-localization of membranes from all the three biomarkers. It requires advanced color unmixing for creating equivalent singleplex images (referred as synthetic singleplexes) from each triplex image for each biomarker. Methods: We explored different unsupervised methods for unmixing cMET-PDL1-EGFR images. Initially we explored an unsupervised method based on Lee et al. [1], which formulated the color unmixing problem as a non-negative matrix factorization (NMF) method and proposed a system capable of performing the color decomposition in a fully automated manner, where no reference stain color selection is required. Next, we developed cycle-Generative Adversarial (cycle-GAN) [2] models, for each of the three stains – TAMRA (purple), QM-Dabsyl (yellow) and Green. The models were trained on 6 cases of lung having different intensities of the stains. Results: The NMF and cycle-GAN method was validated on 5400 lung images. On analysis of the results and on review with pathologists, we observed that NMF was able to produce reasonable results on synthetic PDL1 and EGFR, but the synthetic Green images did not replicate the adjacent Green images properly. On the other hand, cycle-GAN was able to generate similar synthetic images for all three stains as demonstrated by the similarity metrics in Table 1. Pathologist review of the cycle-GAN results determined that the difference in percentage scores between pairs of adjacent and synthetic singleplex images would be within the range 2%-5% only. Conclusions: In this project, we performed detailed analysis of two unsupervised methods for color unmixing on triplex images. On comparison of the methods based on image similarity measures and pathologist review, we conclude that the cycle-GAN method is competent in generating synthetic images. References: [1] Lee, Daniel, and H. Sebastian Seung, "Algorithms for non-negative matrix factorization." Advances in neural information processing systems 13 (2000). [2] Jun-Yan Zhu, Taesung Park, Phillip Isola, and Alexei A Efros. 2017. Unpaired image-to-image translation using cycle-consistent adversarial networks. In ICCV. 2223–2232.[Table: see text]
Phase II trial of lazertinib in patients with epidermal growth factor receptor (EGFR) mutation-positive (M+), metastatic non-small cell lung cancer (NSCLC) with asymptomatic or mild symptomatic brain metastases after failure of EGFR tyrosine kinase inhibitor (TKI) (KCSG LU20-15).
Authors: Min Hee Hong, Yoon Ji Choi, Hee Kyung Ahn, Bhumsuk Keam, Yu Jung Kim, Ju Won Kim, Hye Ryun Kim, Jin-Hyoung Kang
Journal: Journal of Clinical Oncology (2023)

9054 Background: Central nervous system (CNS) metastases occur not infrequently, ultimately devastating consequences in advanced EGFR M+ NSCLC. Lazertinib, a 3rd-generation (G) EGFR-TKI, has shown potent antitumor activity in EGFR-mutant NSCLC. We conducted a phase II single-arm study of lazertinib in EGFR M+ NSCLC patients (pts) having CNS metastases to evaluate its CNS activity. Methods: The patients exhibiting CNS progression upon 1st or 2nd-G EGFR-TKIs with least one measurable CNS lesion were enrolled. The primary endpoint was intracranial objective response rate (iORR) in evaluable for response set (ERS). Secondary endpoints included iORR without T790M mutation, overall ORR (oORR), disease control rate (DCR), intracranial progression-free survival (iPFS) in ERS. Overall survival (OS) and safety analyses were performed in pts who received at least one dose of lazertinib. Cerebrospinal fluid (CSF) penetration was measured as exploratory biomarker study. Results: Of 40 pts enrolled, 38 were evaluable for tumor response. Nineteen pts harbored exon 19 deletion and 21 pts for exon 21 L858R and 30% of pts had radiologic evidence of leptomeningeal carcinomatosis (LM) with 2 cytological confirmed cases. Forty-five percent of pts received afatinib as first line treatment, followed by 42.5% of gefitinib and 12.5% of erlotinib. Baseline plasma samples of all the 40 patients obtained for liquid-based next-generation sequencing (Guardant360) and T790M was found in 5 pts prior to lazertinib treatment. iORR was 57.9% (22/38). iORR with T790M-negative, oORR, and DCR were 54.5%, 39.5%, and 97.4%, respectively. With median follow-up of 13.6 months, median iPFS and OS were not reached. Treatment-related adverse events (TRAEs) emerged in 85.0% of pts with most common TRAEs being skin rash (50.0%) and paresthesia (42.5%). Grade 3 or 4 TRAEs were reported in 10.0%. The CSF penetration rates of lazertinib and its metabolite (YH26334) were 46.2% and 33.1%, respectively in paired CSF and plasma samples, suggesting high CNS penetration efficacy. Conclusions: Lazertinib has substantial CNS activity regardless of T790M status against the progression of intracranial metastases ± LM during the treatment of 1 st or 2 nd -G EGFR-TKIs in metastatic EGFR M+ NSCLC pts. These results suggest that using lazertinib instead of brain local treatment would be a potential strategy in EGFR M+ NSCLC, who progressed on CNS metastases after prior EGFR-TKI. Clinical trial information: NCT05326425 . [Table: see text]
Outcomes of stage IV non-small cell lung cancer patients after failure of platinum-based chemotherapy in clinical trials and real-world settings: A literature review.
Authors: Yu Yang Soon, Wesley Furnback, Jin Kim, Jenny Chuang, Gordon Chavez, Christina Proescholdt, Cloe Ying Chee Koh
Journal: Journal of Clinical Oncology (2023)

e18859 Background: To report the outcomes of therapeutic regimens being evaluated for patients with stage IV non-small cell lung cancer (NSCLC) that has progressed on or after platinum-based chemotherapy in clinical trial and real-world settings. Methods: A systematic literature review was undertaken to identify clinical trials and real-world studies evaluating treatments for stage IV NSCLC after progression with platinum-based chemotherapy. Studies were included in the review if they were published between September 2017 and September 2021, in English, and included an outcome of interest. The outcomes of interest were overall response rate, progression-free survival, overall survival, the incidence of grade 3-4 adverse events, and discontinuation due to adverse events. Results: A total of 23 studies were identified, comprising of 17 clinical trials and six real-world studies. The total sample size ranged from 12 to 1,253 patients in clinical trials and 11 to 383 patients in real-world studies. A total of 28 and six treatment regimens were evaluated within the clinical trials and real-world studies respectively. Six clinical trials evaluated outcomes in the second-line setting, one in the third-line, three in a mix of second-line and above, and seven did not report the specific treatment line(s). There were no real-world studies exclusively in the second-line setting, one in the third-line, three in a mix of second-line and above, and two did not report the specific treatment line(s). Ramucirumab + docetaxel was the only treatment regimen evaluated in both the clinical trial and real-world studies. In the real-world studies, nivolumab was the most common treatment evaluated (n = 3). The real-world studies were conducted in India (n = 2), China, Colombia, Germany, and the United States. The overall response rate (ORR) ranged from 3% to 66% and a rate of &gt; 15% was reported for one or more treatment regimens in 86% (12/14) of clinical trials. ORR ranged from 10% to 36% in real-world studies. Median progression-free survival ranged from 1 to 5 months in clinical trials and 3 to 8 months in real-world studies. In clinical trials, a median PFS of &gt; 6 months was observed in 71% (10/14) of studies. Median overall survival (OS) ranged from 5 to 15 months in clinical trials and 3 to 18 months in real-world studies. Discontinuation due to adverse events ranged from 3-15% in clinical trials and 9-20% in real-world studies. Conclusions: Patients with stage IV NSCLC that has progressed on or after platinum-based chemotherapy experienced a limited response and a high burden of adverse events with the treatment regimens evaluated in both the clinical trial and real-world settings.
Clinical characteristics of patients with non-small cell lung cancer eligible for biology-guided radiotherapy.
Authors: Santiago Olaechea, Tidie Song, Linda Gilmore, Rodney E. Infante, Kenneth D. Westover, Yuanyuan Zhang, Neil B. Desai, Tu Dan, Robert D. Timmerman, Orhan K. Oz, Puneeth Iyengar, Aurelie Garant
Journal: Journal of Clinical Oncology (2023)

e20523 Background: Biology-guided radiotherapy (BgRT) is a novel radiotherapy modality that uses real-time positron emission tomography (PET) to guide radiotherapy beamlets. BgRT recently received FDA clearance for clinical use using the 18F FDG radiotracer for the treatment of tumors in lung and bone. We sought to identify non-small cell lung cancer (NSCLC) patients who may be candidates for BgRT based on diagnostic FDG PET/CT imaging. Methods: We conducted an IRB-approved retrospective assessment of NSCLC patients diagnosed between 01/01/2006 and 12/31/2013 at a tertiary care center in the United States. Patient and tumor characteristics were verified by an institutional data repository team and through electronic medical record review. Patients were excluded from analysis when documentation of clinical/ imaging findings was insufficient. Frequency of characteristics were interpreted with and without tumor diameter and maximum standardized uptake value (SUV Max ) parameters, to confirm eligibility for BgRT on this novel radiotherapy device. Results: Of the 686 patients eligible for analysis, 523 presented with tumor SUV Max of ≥6 on diagnostic PET imaging and 360 presented with tumor diameters of at least 2 cm and below 5 cm. Of the 277 patients who met both SUV Max and size parameters, respectively, 75 (27.1%), 145 (52.3%), and 57 (20.6%) presented with squamous, adenocarcinoma, or other/unknown histology, and 77 (27.9%), 29 (10.5%), 92 (33.3%), and 78 (28.3%) presented with stage I, II, III, or IV tumors (AJCC 7 th edition). Conclusions: Theoretical applicability of biology-guided radiotherapy was observed in our NSCLC patient cohort. Therefore, despite current limitations of radiotracer uptake thresholds and tumor size restrictions, there is broad potential applicability of this treatment modality, either as a single modality treatment or in conjunction with active systemic therapy. [Table: see text]
The brown university cancer prevention and survivorship curriculum: A case study on program development in an internal medicine residency.
Authors: Elizabeth Francis, Tamar Pounardjian, Jennifer Li, Prashanth Moku, Olivia Avidan, Kathryn DeCarli, Ellen F. Manzullo, Tara B. Sanft, Kelly McGarry, Don S. Dizon, Christine Mary Duffy
Journal: Journal of Clinical Oncology (2023)

11031 Background: Advances in screening, early detection, and treatment have increased the number of cancer survivors. Cancer survivors have a unique set of medical, psychosocial, physical, and financial challenges. Though it is critical for provider teams to be attuned and equipped to address these issues, we identified two training programs in this discipline. Medical residency clinical education does not fully explore the role of cancer preventative services and survivorship experiences available to patients and their families. We developed an elective at Alpert Medical School at Brown University/Lifespan Internal Medicine Residency Program (Brown) to improve medicine residents’ knowledge and clinical skills on different aspects of the cancer control continuum, with a focus on prevention, early detection, survivorship and surveillance. Methods: In 2020, a team of Brown internal medicine (IM) residents, faculty and one hematology oncology (heme/onc) fellow examined the existing cancer prevention and survivorship infrastructure, identified key faculty and clinics, and examined existing programs at peer institutions. A needs assessment was completed by Brown IM residents and heme/onc fellows. We then designed the Cancer Prevention &amp; Survivorship Elective, an innovative and novel educational elective for medical residents to promote interest, awareness, and understanding of cancer prevention and survivorship. The 6 module one month elective features didactics and clinical experiences offered via a live and independent study fashion. The elective brought together 27 disciplines, 64 faculty lecturers from 10 peer institutions across the United States and included 20 unique clinics. Residents completed anonymous pre- and post-course surveys to measure their understanding and degree of confidence in different aspects of cancer prevention and survivorship, not limited to surveillance, health disparities and global perspective, primary and secondary prevention, late and long-term effects, and quality of life. Results: In January 2023, ten residents, ranging from first- to third-year IM and medicine-pediatrics, participated in the live elective. Two IM residents have registered to complete the elective via independent study in 2023. To date, the Cancer Prevention and Survivorship Elective has improved IM residents’ confidence, comfort and clinical skills in treating patients along the cancer care continuum. Conclusions: This curricula serves as an example for inter-institutional collaboration, and highlights the need for a multidisciplinary approach when caring for patients at high-risk of developing cancer and surviving cancer.